Abstract
HOX transcription factors and their cofactors, MEINOX, are critical regulators of positional identity and cellular plasticity. While their functions are essential during embryonic development, they also play key roles in maintaining adult tissue homeostasis. Dysregulation of HOX and MEINOX has been implicated in the pathogenesis of various diseases, including fibrosis and cancer. This review explores the contributions of HOX and MEINOX to dedifferentiation and cellular reprogramming, processes that drive fibrotic disease onset and cancer progression. It also addresses their role in extracellular matrix remodeling in these conditions. Particular attention is given to their involvement in epithelial-mesenchymal transition, where altered HOX and MEINOX expression promotes phenotypic plasticity, cancer invasiveness, and fibrotic tissue remodeling. By integrating these perspectives, this review underscores the significance of HOX-MEINOX dysregulation and altered positional identity in disease progression. Targeting this dysregulation may offer innovative strategies to modulate epithelial-mesenchymal transition and extracellular matrix dynamics, presenting new therapeutic opportunities for combating fibrosis and cancer.